tbuckley/cabot-search huggingface dataset:
Intergenic Regions of Saccharomycotina Yeasts are Enriched in Potential to Encode Transmembrane Domains
Authors: Emilios Tassios, Christoforos Nikolaou, Nikolaos Vakirlis
Journal: Molecular Biology and Evolution (2023)

Intergenic genomic regions have essential regulatory and structural roles that impose constraints on their sequences. But regions that do not currently encode proteins also carry the potential to do so in the future. De novo gene emergence, the evolution of novel genes out of previously noncoding sequences has now been established as a potent force for genomic novelty. Recently, it was shown that intergenic regions in the genome of Saccharomyces cerevisiae harbor pervasive cryptic potential to, if theoretically translated, form transmembrane domains (TM domains) more frequently than expected by chance given their nucleotide composition, a property that we refer to as TM-forming enrichment. The source and biological relevance of this property is unknown. Here, we expand the investigation into the TM-forming potential of intergenic regions to the entire Saccharomycotina budding yeast subphylum, in an effort to explain this property and understand its importance. We find pervasive but variable enrichment in TM-forming potential across the subphylum regardless of the composition and average size of intergenic regions. This cryptic property is evenly spread across the genome, cannot be explained by the hydrophobic content of the sequence, and does not appear to localize to regions containing regulatory motifs. This TM-forming enrichment specifically, and not the actual TM-forming potential, is associated, across genomes, with more TM domains in evolutionarily young genes. Our findings shed light on this newly discovered feature of yeast genomes and constitute a first step toward understanding its evolutionary importance.
Immune response evolution in peanut epicutaneous immunotherapy for <scp>peanut‐allergic</scp> children
Authors: Marie Bastin, Warner W. Carr, Carla M. Davis, David M. Fleischer, Jay A. Lieberman, S. Shahzad Mustafa, Thibault Helleputte, Timothée Bois, Dianne E. Campbell, Todd D. Green, Matthew Greenhawt
Journal: Allergy (2023)

Epicutaneous immunotherapy with investigational Viaskin™ Peanut 250 μg (DBV712) has demonstrated statistically superior desensitization versus placebo in peanut-allergic children in clinical trials. It is unclear whether serologic biomarkers predict response.Serum-specific IgG4 and IgE (whole peanut and components) from subjects enrolled in the phase 3 Efficacy and Safety of Viaskin Peanut in Children With IgE-Mediated Peanut Allergy study were examined by exploratory univariate and multivariate analyses to determine trajectories and predictors of treatment response, based upon peanut protein eliciting dose (ED) at Month (M) 12 double-blind placebo-controlled food challenge.Among Viaskin Peanut-treated subjects, peanut sIgG4 significantly increased from baseline through M12 and peanut sIgE peaked at M3 and fell below baseline by M12, with sIgG4 and sIgE peanut components mirroring these trajectories. Placebo subjects had no significant changes. By univariate analysis, M12 peanut sIgG4/sIgE was higher in treatment responders (p < 0.001) and had highest area under the curve (AUC) for predicting ED ≥300 mg and ≥1000 mg (AUC 69.5% and 69.9%, respectively). M12 peanut sIgG4/sIgE >20.1 predicted M12 ED ≥300 mg (80% positive predictive value). The best performing component was Ara h 1 sIgE <15.7 kUA /L (AUC 66.5%). A multivariate model combining Ara h 1 and peanut sIgG4/sIgE had an AUC of 68.2% (ED ≥300 mg) and 67.8% (ED ≥1000 mg).Peanut sIgG4 rise most clearly differentiated Viaskin Peanut versus placebo subjects. sIgG4/sIgE ratios >20.1 and the combination of Ara h 1 and peanut sIgG4/sIgE had moderate ability to predict treatment response and could potentially be useful for clinical monitoring. Additional data are needed to confirm these relationships.
Comment on ‘study and validation of an explainable machine learning-based mortality prediction following emergency surgery in the elderly: a prospective observational study’
Authors: Juanqing Zheng
Journal: International Journal of Surgery (2023)

Department of Cardiology, YiWu Central Hospital, Zhejiang 322000, China Running Title: machine learning and emergency surgery. Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article. Published online ■ ■ *Corresponding author. Address: Department of Cardiology, YiWu Central Hospital, Zhejiang 322000, China. E-mail address: [email protected] (J. Zheng). This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0/
Spinal Cord Burst Stimulation vs Placebo Stimulation for Patients With Chronic Radicular Pain After Lumbar Spine Surgery
Authors: Akash Goel, Michael Leong, Harsha Shanthanna
Journal: JAMA (2023)

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Bipotent transitional liver progenitor cells contribute to liver regeneration
Authors: Wenjuan Pu, Huan Zhu, Mingjun Zhang, Monika Pikiolek, Caner Ercan, Jie Li, Xiuzhen Huang, Ximeng Han, Zhenqian Zhang, Zan Lv, Yan Li, Kuo Liu, Lingjuan He, Xiuxiu Liu, Markus H. Heim, Luigi M. Terracciano, Jan S. Tchorz, Bin Zhou
Journal: Nature Genetics (2023)

Abstract Following severe liver injury, when hepatocyte-mediated regeneration is impaired, biliary epithelial cells (BECs) can transdifferentiate into functional hepatocytes. However, the subset of BECs with such facultative tissue stem cell potential, as well as the mechanisms enabling transdifferentiation, remains elusive. Here we identify a transitional liver progenitor cell (TLPC), which originates from BECs and differentiates into hepatocytes during regeneration from severe liver injury. By applying a dual genetic lineage tracing approach, we specifically labeled TLPCs and found that they are bipotent, as they either differentiate into hepatocytes or re-adopt BEC fate. Mechanistically, Notch and Wnt/β-catenin signaling orchestrate BEC-to-TLPC and TLPC-to-hepatocyte conversions, respectively. Together, our study provides functional and mechanistic insights into transdifferentiation-assisted liver regeneration.
Mimicking the Graded Wavy Structure of the Anterior Cruciate Ligament
Authors: Sandra Camarero‐Espinosa, Huipin Yuan, Pieter J. Emans, Lorenzo Moroni
Journal: Advanced Healthcare Materials (2023)

Anterior cruciate ligament (ACL) is the connective tissue providing mechanical stability to the knee joint. ACL reconstruction upon rupture remains a clinical challenge due to the high mechanical properties required for proper functioning. ACL owes its outstanding mechanical properties to the arrangement of the extracellular matrix (ECM) and to the cells with distinct phenotypes present along the length of the tissue. Tissue regeneration appears as an ideal alternative. In this study, a tri-phasic fibrous scaffold that mimics the structure of collagen in the native ECM is developed, presenting a wavy intermediate zone and two aligned uncurled extremes. The mechanical properties of the wavy scaffolds present a toe region, characteristic of the native ACL, and an extended yield and ultimate strain compared to aligned scaffolds. The presentation of a wavy fiber arrangement affects cell organization and the deposition of a specific ECM characteristic of fibrocartilage. Cells cultured in wavy scaffolds grow in aggregates, deposit an abundant ECM rich in fibronectin and collagen II, and express higher amounts of collagen II, X, and tenomodulin as compared to aligned scaffolds. In vivo implantation in rabbits shows a high cellular infiltration and the formation of an oriented ECM compared to aligned scaffolds.
NAD+ precursor supplementation prevents mtRNA/RIG-I-dependent inflammation during kidney injury
Authors: Tomohito Doke, Sarmistha Mukherjee, Dhanunjay Mukhi, Poonam Dhillon, Amin Abedini, James G. Davis, Karthikeyani Chellappa, Beishan Chen, Joseph A. Baur, Katalin Susztak
Journal: Nature Metabolism (2023)
Association of Antenatal COVID-19–Related Stress With Postpartum Maternal Mental Health and Negative Affectivity in Infants
Authors: Susanne Schweizer, Jack L. Andrews, Karina Grunewald, Levi Kumle, Savannah Minihan, Annabel Songco, Elaine Fox, Cecile D. Ladouceur, Louise Mewton, Michelle Moulds, Jennifer H. Pfeifer, Anne-Laura van Harmelen
Journal: JAMA Network Open (2023)

Importance Antenatal stress is a significant risk factor for poor postpartum mental health. The association of pandemic-related stress with postpartum outcomes among mothers and infants is, however, less well understood. Objective To examine the association of antenatal COVID-19–related stress with postpartum maternal mental health and infant outcomes. Design, Setting, and Participants This cohort study was conducted among 318 participants in the COVID-19 Risks Across the Lifespan study, which took place in Australia, the UK, and the US. Eligible participants reported being pregnant at the first assessment wave between May 5 and September 30, 2020, and completed a follow-up assessment between October 28, 2021, and April 24, 2022. Main Outcomes and Measures COVID-19–related stress was assessed with the Pandemic Anxiety Scale (score range, 0-4, with higher scores indicating greater COVID-19–related stress). The 8-item Patient Health Questionnaire (score range, 0-3, with higher scores indicating more frequent symptoms of depression) was used to measure maternal depression at each time point, and the 7-item General Anxiety Disorder scale (score range, 0-3, with higher scores indicating more frequent symptoms of anxiety) was used to measure generalized anxiety at each time point. At follow-up, postpartum distress was assessed with the 10-item Postpartum Distress Measure (score range, 0-3, with higher scores indicating greater postpartum distress), and infant outcomes (negative and positive affectivity and orienting behavior) were captured with the Infant Behavior Questionnaire (score range, 1-7, with higher scores indicating that the infant exhibited that affect/behavior more frequently). Results The study included 318 women (mean [SD] age, 32.0 [4.6] years) from Australia (88 [28%]), the US (94 [30%]), and the UK (136 [43%]). Antenatal COVID-19–related stress was significantly associated with maternal postpartum distress (β = 0.40 [95% CI, 0.28-0.53]), depression (β = 0.32 [95% CI, 0.23-0.41]), and generalized anxiety (β = 0.35 [95% CI, 0.26-0.44]), as well as infant negative affectivity (β = 0.45 [95% CI, 0.14-0.76]). The findings remained consistent across a range of sensitivity analyses. Conclusions and Relevance The findings of this cohort study suggest that targeting pandemic-related stressors in the antenatal period may improve maternal and infant outcomes. Pregnant individuals should be classified as a vulnerable group during pandemics and should be considered a public health priority, not only in terms of physical health but also mental health.
Significance of anatomical resection and resection margin status in patients with HBV-related hepatocellular carcinoma and microvascular invasion: a multicenter propensity score-matched study
Authors: Xiu-Ping Zhang, Shuai Xu, Zhao-Yi Lin, Qing-Lun Gao, Kang Wang, Zi-Li Chen, Mao-Lin Yan, Fan Zhang, Yu-Fu Tang, Zhi-Ming Zhao, Cheng-Gang Li, Wan Yee Lau, Shu-Qun Cheng, Ming-Gen Hu, Rong Liu
Journal: International Journal of Surgery (2023)

Microvascular invasion (MVI) is a risk factor for postoperative survival outcomes for patients with hepatocellular carcinoma (HCC) after hepatectomy. This study aimed to evaluate the impact of anatomical resection (AR) versus nonanatomical resection (NAR) combined with resection margin (RM) (narrow RM <1 cm vs. wide RM ≥1 cm) on long-term prognosis in hepatitis B virus-related HCC patients with MVI.Data from multicenters on HCC patients with MVI who underwent hepatectomy was analyzed retrospectively. Propensity score matching analysis was performed in these patients.The 1965 enrolled patients were divided into four groups: AR with wide RM ( n =715), AR with narrow RM ( n =387), NAR with wide RM ( n =568), and NAR with narrow RM ( n =295). Narrow RM ( P <0.001) and NAR ( P <0.001) were independent risk factors for both overall survival and recurrence-free survival in these patients based on multivariate analyses. For patients in both the AR and NAR groups, wide RM resulted in significantly lower operative margin recurrence rates than those patients in the narrow RM groups after propensity score matching ( P =0.002 and 0.001). Patients in the AR with wide RM group had significantly the best median overall survival (78.9 vs. 51.5 vs. 48.0 vs. 36.7 months, P <0.001) and recurrence-free survival (23.6 vs. 14.8 vs. 17.8 vs. 9.0 months, P <0.001) than those in the AR with narrow RM, NAR with wide RM or with narrow RM groups, respectively.If technically feasible and safe, AR combined with wide RM should be the recommended therapeutic strategy for HCC patients who are estimated preoperatively with a high risk of MVI.
Leveraging a nationwide infection surveillance program to implement a colorectal surgical site infection reduction bundle: a pragmatic, prospective, and multicenter cohort study
Authors: Josep M. Badia, Nares Arroyo-Garcia, Ana Vázquez, Alexander Almendral, Aina Gomila-Grange, Domenico Fraccalvieri, David Parés, Ana Abad-Torrent, Marta Pascual, Alejandro Solís-Peña, Mireia Puig-Asensio, Miguel Pera, Francesc Gudiol, Enric Limón, Miquel Pujol
Journal: International Journal of Surgery (2023)

Bundled interventions usually reduce surgical site infection (SSI) when implemented at single hospitals, but the feasibility of their implementation at the nationwide level and their clinical results are not well established.Pragmatic interventional study to analyze the implementation and outcomes of a colorectal surgery care bundle within a nationwide quality improvement program. The bundle consisted of antibiotic prophylaxis, oral antibiotic prophylaxis (OAP), mechanical bowel preparation, laparoscopy, normothermia, and a wound retractor. Control group (CG) and Intervention group (IG) were compared. Overall SSI, superficial (S-SSI), deep (D-SSI), and organ/space (O/S-SSI) rates were analyzed. Secondary endpoints included microbiology, 30-day mortality, and length of hospital stay.A total of 37 849 procedures were included, 19 655 in the CG and 18 194 in the IG. In all, 5462 SSIs (14.43%) were detected: 1767 S-SSI (4.67%), 847 D-SSI (2.24%), and 2838 O/S-SSI (7.5%). Overall SSI fell from 18.38% (CG) to 10.17% (IG), odds ratio (OR) of 0.503 [0.473-0.524]. O/S-SSI rates were 9.15% (CG) and 5.72% (IG), OR of 0.602 [0.556-0.652]. The overall SSI rate was 16.71% when no measure was applied and 6.23% when all six were used. Bundle implementation reduced the probability of overall SSI (OR: 0.331; CI 95 : 0.242-0.453), and also O/S-SSI rate (OR: 0.643; CI 95 : 0.416-0.919). In the univariate analysis, all measures except normothermia were associated with a reduction in overall SSI, while only laparoscopy, OAP, and mechanical bowel preparation were related to a decrease in O/S-SSI. Laparoscopy, wound retractor, and OAP decreased overall SSI and O/S-SSI in the multivariate analysis.In this cohort study, the application of a specific care bundle within a nationwide nosocomial infection surveillance system proved feasible and resulted in a significant reduction in overall and O/S-SSI rates in the elective colon and rectal surgery. The OR for SSI fell between 1.5 and 3 times after the implementation of the bundle.
Farcimab: a flicker of light in the darkness of neovascular age-related macular degeneration and Diabetes Mellitus – correspondence
Authors: Omer Ahmed Shaikh, Shifa Amin, Gulrukh Shaikh, Kanchan Kumari, Irfan Ullah, Muhammad Sohaib Asghar
Journal: International Journal of Surgery (2023)

Shaikh, Omer Ahmed MBBS; Amin, Shifa MBBS; Shaikh, Gulrukh MBBS; Kumari, Kanchan MBBS; Ullah, Irfan MBBS; Asghar, Muhammad Sohaib MBBS Author Information
Tingible body macrophages: Gargantuan chameleons of the germinal center
Authors: Elisa Madeleine Baudon, Marc Bajenoff
Journal: The Journal of Experimental Medicine (2023)

Tingible body macrophages in lymph node are involved in cleaning up debris from apoptotic B cells. Gurwisz et al. (2023. J. Exp. Med.https://doi.org/10.1084/jem.20222173) and Grootveld et al. (2023. Cell.https://doi.org/10.1016/j.cell.2023.02.004) report how tingible body macrophages, originating from tissue-resident macrophages, clear apoptotic B cells in the germinal center using a “stand-hunting” strategy.
Medicare Advantage Enrollment Among Beneficiaries With End-Stage Renal Disease in the First Year of the 21st Century Cures Act
Authors: Kevin H. Nguyen, Eunhae G. Oh, David J. Meyers, Daeho Kim, Rajnish Mehrotra, Amal N. Trivedi
Journal: JAMA (2023)

Importance Before 2021, most Medicare beneficiaries with end-stage renal disease (ESRD) were unable to enroll in private Medicare Advantage (MA) plans. The 21st Century Cures Act permitted these beneficiaries to enroll in MA plans effective January 2021. Objective To examine changes in MA enrollment among Medicare beneficiaries with ESRD after enactment of the 21st Century Cures Act overall and by race or ethnicity and dual-eligible status. Design, Setting, and Participants This cross-sectional time-trend study used data from Medicare beneficiaries with ESRD (both kidney transplant recipients and those undergoing dialysis) between January 2019 and December 2021. Data were analyzed between June and October 2022. Exposures 21st Century Cures Act. Main Outcomes and Measures Primary outcomes were the proportion of Medicare beneficiaries with prevalent ESRD who switched from traditional Medicare to MA between 2020 and 2021 and those with incident ESRD who newly enrolled in MA in 2021. Individuals who stayed in traditional Medicare were enrolled in 2020 and 2021 and those who switched to MA were enrolled in traditional Medicare in 2020 and MA in 2021. Results Among 575 797 beneficiaries with ESRD in 2020 or 2021 (mean [SD] age, 64.7 [14.2] years, 42.2% female, 34.0% Black, and 7.7% Hispanic or Latino), the proportion of beneficiaries enrolled in MA increased from 24.8% (December 2020) to 37.4% (December 2021), a relative change of 50.8%. The largest relative increases in MA enrollment were among Black (72.8% relative increase), Hispanic (44.8%), and dual-eligible beneficiaries with ESRD (73.6%). Among 359 617 beneficiaries with TM and prevalent ESRD in 2020, 17.6% switched to MA in 2021. Compared with individuals who stayed in traditional Medicare, those who switched to MA had modestly more chronic conditions (6.3 vs 6.1; difference, 0.12 conditions [95% CI, 0.10-0.16]) and similar nondrug spending in 2020 (difference, $509 [95% CI, −$58 to $1075]) but were more likely to be Black (difference, 19.5 percentage points [95% CI, 19.1-19.9]) and have dual Medicare-Medicaid eligibility (difference, 20.8 percentage points [95% CI, 20.4-21.2]). Among beneficiaries who were newly eligible for Medicare ESRD benefits in 2021, 35.2% enrolled in MA. Conclusions and Relevance Results suggest that increases in MA enrollment among Medicare beneficiaries with ESRD were substantial the first year after the 21st Century Cures Act, particularly among Black, Hispanic, and dual-eligible individuals. Policy makers and MA plans may need to assess network adequacy, disenrollment, and equity of care for beneficiaries who enrolled in MA.
The future of HIV testing in eastern and southern Africa: Broader scope, targeted services
Authors: Anna Grimsrud, Lynne Wilkinson, Peter Ehrenkranz, Stephanie Behel, Thato Chidarikire, Tina Chisenga, Rachel Golin, Cheryl Case Johnson, Maureen Milanga, Obinna Onyekwena, Maaya Sundaram, Vincent Wong, Rachel Baggaley
Journal: PLoS Medicine (2023)

Scale-up of HIV testing services (HTS), primarily through routine offer of HIV testing in health services, has led to an increase in the proportion of people with HIV who know their status and are accessing HIV treatment.• In eastern and southern Africa (ESA), home to more than half of people living with HIV globally, many countries are close to reaching global targets for HIV treatment and viral suppression, with slower progress towards the global target that 95% of people should know their HIV status.Given this, it is critical to update the approach to HIV testing to reflect changes in the HIV epidemic, the response to it, and to acknowledge ongoing resource constraints.• An expert consultation series defined this updated approach as a shift to "broader scope, targeted services."Over the next decade, HTS in ESA should implement a status-neutral approach that maintains core testing services to reach the greatest number of people with HIV not on treatment, while broadening the scope to support linkage to appropriate prevention and treatment.It is important that HTS programs use a strategic mix of modalities focused on people most likely to have undiagnosed HIV, those who are not on ART, and people who are more vulnerable to HIV acquisition.• Ten key themes for the future of HTS were articulated.The most critical are: promote a status-neutral approach to HTS; realize the potential of HIV self-testing (HIVST); prioritize facility-based HTS; reframe retesting among those previously diagnosed but not currently on antiretroviral therapy (ART) as an opportunity; and involve and invest in community leadership and community-led monitoring (CLM) to ensure HTS meets the needs and preferences of clients.